E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Retinitis Pigmentosa (RP) due to Mutations in Exon 13 of the USH2A Gene |
retinitis pigmentosa (RP) como consecuencia de mutaciones en el exón 13 del gen USH2A |
|
E.1.1.1 | Medical condition in easily understood language |
RP due to Mutations in Exon 13 of the USH2A Gene |
RP como consecuencia de mutaciones en el exón 13 del gen USH2A |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038914 |
E.1.2 | Term | Retinitis pigmentosa |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of QR-421a |
Evaluar la eficacia de QR-421a |
|
E.2.2 | Secondary objectives of the trial |
To further evaluate efficacy To evaluate the safety and tolerability of QR-421a To evaluate changes in Patient-Reported Outcome (PRO) measures in subjects treated with QR-421a To evaluate systemic exposure of QR-421a |
Seguir evaluando la eficacia Evaluar la seguridad y tolerabilidad de QR-421a Evaluar los cambios en las mediciones del Resultado percibido por el paciente (RPP) en sujetos tratados con QR-421a Evaluar la exposición sistémica de QR-421a |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- An adult (≥ 18 years) willing and able to provide informed consent for participation prior to performing any study related procedure. OR A minor able to complete all study assessments and comply with the protocol and has a parent or caregiver willing and able to follow study instructions, and attend study visits with the subject as required. - Clinical presentation consistent with RP with Usher syndrome type 2 or non-syndromic form of RP (NSRP), based on ophthalmic, audiologic, and vestibular examinations. - A molecular diagnosis of homozygosity or compound heterozygosity for 1 or more pathogenic exon 13 mutations in the USH2A gene, based on genetic analysis at screening. - Reliable BCVA, perimetry, and other measurements in both eyes. |
-Un adulto (≥18 años) con voluntad y capacidad para proporcionar consentimiento informado para participar antes de que se realice cualquier procedimiento relacionado con el estudio. O BIEN Un menor (12 a <18 años) con padre o tutor legal con voluntad y capacidad para proporcionar permiso escrito para la participación del sujeto antes de realizar cualquier procedimiento relacionado con el estudio y sujetos pediátricos capaces de proporcionar asentimiento adecuado para su edad para participar en el estudio. -Presentación clínica coherente con la RP con síndrome de Usher tipo 2 o una forma no sindrómica de RP (non- syndromic form of RP, NSRP), en función de exámenes oftálmicos, audiológicos y vestibulares. -Un diagnóstico molecular de homocigosidad o heterocigosidad compuesta para una o más mutaciones patogénicas del exón 13 en el gen USH2A, en función de análisis genéticos durante la selección. -MAVC, perimetría y otras mediciones fiables en ambos ojos. |
|
E.4 | Principal exclusion criteria |
- Presence of any significant ocular or non-ocular disease/disorder (or medication and/or laboratory test abnormalities) which, in the opinion of the Investigator and with concurrence of the Medical Monitor, may either put the subject at risk because of participation in the study, may influence the results of the study, or the subject’s ability to participate in the study. - Known hypersensitivity to antisense oligonucleotides or any constituents of the injection. |
-La presencia de cualquier trastorno/enfermedad ocular o no ocular de importancia (o medicación o anormalidades en análisis de laboratorio) que, en la opinión del investigador y con el acuerdo del supervisor médico, pueda poner al sujeto en riesgo por su participación en el estudio, que pueda afectar los resultados del estudio, o la capacidad del sujeto para participar en el studio. - Hipersensibilidad conocida a oligonucleótidos antisentido o a cualquier componente de la inyección. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in best corrected visual acuity (BCVA) (based on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart) at 18 months of treatment versus sham-procedure |
Cambio desde los valores iniciales en la mejor agudeza visual corregida (MAVC) (en función del gráfico Estudio sobre tratamiento precoz de la retinopatía diabética [Early Treatment Diabetic Retinopathy Study, ETDRS]) a los 18 meses de tratamiento en comparación con el procedimiento simulado |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At multiple timepoints up to 18 months |
En múltiples puntos de tiempo hasta 18 meses |
|
E.5.2 | Secondary end point(s) |
Key Secondary endpoints: - Proportion of patients who maintain vision defined by BCVA loss less than 15 Letters (ETDRS)
Other Secondary endpoints: - Change from baseline in the following outcome measures: Other measures of BCVA Spectral domain optical coherence tomography (SD-OCT) Low Luminance Visual Acuity (LLVA) Microperimetry Static perimetry Full-field Stimulus Threshold (FST) -Change from baseline in PRO measures, as assessed by: Veteran Administration Low Vision Visual Functioning Questionnaire (VA LV VFQ-20) (Stelmack 2007) Patient Global Impressions of Severity (PGI-S) Patient Global Impressions of Change (PGI-C) -Ocular and non-ocular adverse events (AEs) -Exposure of QR-421a in serum |
Criterios de valoración secundarios clave: -Proporción de pacientes que mantienen la visión según se define por una pérdida de MAVC menor a 15 letras (ETDRS)
Otros criterios de valoración secundarios -Cambio desde los valores iniciales en las siguientes mediciones de resultados: o Otras mediciones de MAVC o Tomografía de coherencia óptica de dominio espectral (Spectral domain optical coherence tomography, SD-OCT) o Agudeza visual de baja luminancia (Low Luminance Visual Acuity, LLVA) o Microperimetría o Perimetría estática o Umbral de estímulo de campo completo (Full-field Stimulus Threshold, FST)
-Cambio desde los valores iniciales en mediciones del RPP, según las siguientes evaluaciones: o Cuestionario de función visual de baja visión de la Administración de Veteranos (VA LV VFQ-20) (Stelmack 2007) o Impresiones globales de la gravedad según el paciente (Patient Global Impressions of Severity, PGI-S) o Impresiones globales de cambio según el paciente (Patient Global Impressions of Change, PGI-C)
-Eventos adversos oculares y no oculares (EA) -Exposición de QR-421a en Suero |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At multiple timepoints up to 24 months |
En múltiples puntos de tiempo hasta 24 meses |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability |
Tolerabilidad |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
estudio de múltiples dosis |
Multiple-Dose Study |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
procedimiento simulado |
Sham |
|
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
Canada |
United States |
United Kingdom |
European Union |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |